Consumer medicine information

Travatan

Travoprost

BRAND INFORMATION

Brand name

Travatan Eye Drops

Active ingredient

Travoprost

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Travatan.

SUMMARY CMI

Travatan®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Travatan?

Travatan contains the active ingredient Travoprost. Travatan is used to treat certain eye conditions such as high pressure inside your eye and open angle glaucoma (an eye condition caused by fluid buildup that damages the optic nerve).

For more information, see Section 1. Why am I using Travatan? in the full CMI.

2. What should I know before I use Travatan?

Do not use if you have ever had an allergic reaction to Travatan or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Travatan? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Travatan and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Travatan?

  • Put one drop of Travatan into the affected eye(s) each day.
  • Follow the instructions provided and use Travatan until your doctor tells you to stop.

More instructions can be found in Section 4. How do I use Travatan? in the full CMI.

5. What should I know while using Travatan?

Things you should do
  • Remind any doctor, dentist, pharmacist or specialist you visit that you are using Travatan.
  • Remove soft contact lenses before using Travatan.
  • Tell your doctor immediately if you develop any signs of an allergic reaction.
Things you should not do
  • Do not stop using this medicine suddenly.
  • Do not use Travatan in children..
  • Do not touch the dropper tip with your fingers or to your eye or any other surface.
Driving or using machines
  • Travatan may cause temporary blurred vision in some people.
  • Be careful before you drive or use any machines or tools until you know how Travatan affects you.
Looking after your medicine
  • Store below 30°C

For more information, see Section 5. What should I know while using Travatan? in the full CMI.

6. Are there any side effects?

Common side effects include itchy eyes, redness of the eye(s), eye pain, eye discharge, eye irritation, feeling that something is in your eye(s), reduced vision, headache.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Travatan® 0.004% Eye Drops Solution

Active ingredient: Travoprost

Consumer Medicine Information (CMI)

This leaflet provides important information about using Travatan. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Travatan.

Where to find information in this leaflet:

1. Why am I using Travatan?
2. What should I know before I use Travatan?
3. What if I am taking other medicines?
4. How do I use Travatan?
5. What should I know while using Travatan?
6. Are there any side effects?
7. Product details

1. Why am I using Travatan?

Travatan contains the active ingredient Travoprost. It belongs to a class of drugs called Prostaglandin analogs.

Travatan is used to treat certain types of eye conditions such as high pressure inside your eye and open angle glaucoma (an eye condition caused by fluid buildup that damages the optic nerve).

Travatan helps to lower the increased eye pressure by increasing the amount of fluid that drains from the eye. It is used either alone or in combination with other medicines or eye drops.

2. What should I know before I use Travatan?

Warnings

Do not use Travatan:

  • If you are allergic to Travoprost, or any of the ingredients listed at the end of this leaflet. Always check the ingredients to make sure you can use this medicine. Symptoms of an allergic reaction may include shortness of breath, difficulty breathing, swelling of the face, lips, tongue or other parts of the body, rash, hives.
  • If you are pregnant or planning to become pregnant.

Check with your doctor if you:

  • have any medical conditions such as any problems with your eye lens or narrow angle glaucoma (an eye condition that occurs when the structure inside the eye which allows the fluid to drain normally becomes restricted).
  • take any medicines for any condition.
  • suffer from any swelling of the eye or any diseases of the cornea.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Travatan should not be used in pregnancy or in women planning to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Travatan is not recommended to be used while breastfeeding.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with Travatan and affect how it works.

Check with your doctor if you take any medicines to treat glaucoma or any other medicines or eye drops.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Travatan.

4. How do I use Travatan?

How much to use

  • Put one drop of Travatan into the affected eye(s) each day.
  • Follow the instructions provided and use Travatan until your doctor tells you to stop.
  • If you are using any other eye drops, use the eye drops at least 5 minutes apart.
  • Tell your doctor or pharmacist if you do not understand your dose.

When to use Travatan

  • Travatan should be used at the same time each day, unless your doctor tells you otherwise.
  • Maximum effect is obtained if the dose is used in the evening.

How to use Travatan

  • Sitting or lying down position might make the process simpler.
  • Remove contact lenses if you are wearing them before putting in the eye drops.
  • Shake the bottle well prior to use.

Follow the steps below to use Travatan:

  • Wash your hands thoroughly with soap and water.
  • Before using a bottle for the first time, tear off the overwrap pouch and take the bottle out (refer diagram 1).

  • Remove the cap from the bottle.
  • Mix the contents of the bottle by inverting 5 to 10 times.
  • Hold the bottle upside down in one hand between your thumb and middle finger (refer diagram 2).

  • Tilt your head back, gently pull down the lower eyelid of your eye to form a pouch/pocket.
  • Place the tip of the bottle close to your eye. Do not touch the tip to your eye as this may cause injury to the eye.
  • Do not touch the dropper tip to eyelid or surrounding areas or any surface to avoid contamination of the dropper tip and solution.
  • Release one drop into the pouch/pocket formed between your eye and eyelid by gently tapping or pressing the base of the bottle with your forefinger (refer diagrams 3 and 4).

  • Gently close your eye. Do not blink or rub your eye.
  • When your eye is closed, place your index finger against the inside corner of your eye and press against your nose for about two minutes. This may result in less side effects by preventing the medicine from draining through the tear duct to the nose and throat, from where it can be absorbed into other parts of your body.
  • This will also help to prevent the unpleasant taste sensation that some people experience while using these eye drops.
  • If necessary, repeat the above steps for the other eye.
  • You may feel a slight burning sensation in the eye shortly after using Travatan. If it continues, or is uncomfortable, contact your doctor or pharmacist.
  • If you want to use any other eye drops wait at least 5 minutes after putting Travatan in.
  • It is normal for a small amount of the eye drops to spill onto your cheek since your eyelids can only hold less than one drop at a time. Wipe away any spillage with a tissue.
  • Replace the cap on the bottle and close it tightly.
  • Always keep the bottle tightly closed when not in use.
  • Wash your hands again with soap and water to remove any residue.
  • Discard the Travatan 4 weeks after opening it.

If you forget to use Travatan

Travatan should be used regularly at the same time each day. If you miss your dose at the usual time, put the drops in as soon as you remember and then go back to using them as recommended by your doctor.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose you missed.

If you use too much Travatan

If you think that you have used too much Travatan, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

If you accidentally put several Travatan drops into your eyes, immediately wash your eyes with warm tap water.

5. What should I know while using Travatan?

Things you should do

Use Travatan only for Eye use.

Remove the soft contact lenses before using Travatan. Put your lenses back in 15 minutes after putting the eye drops in.

Call your doctor straight away if you:

  • notice any change in your eye colour.
  • have any changes in your eyelashes such as increased length, thickness, pigmentation, and/or number of lashes or unwanted hollows of the upper eyelid, eyelid skin darkening after starting the treatment with Travatan.
  • develop any signs of allergic reaction.
  • become pregnant, are planning to become pregnant or if you are breast feeding while using Travatan.

Remind any doctor, dentist, pharmacist or specialist you visit that you are using Travatan.

Things you should not do

  • Do not stop using this medicine suddenly.
  • Do not use Travatan in children.
  • Do not give Travatan to anyone else, even if they seem to have the same condition as you.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Travatan affects you.

Travatan may cause temporary blurred vision in some people after putting the eye drops in..

If so then, wait until your vision clears before driving or using machinery.

Looking after your medicine

  • Store below 30°C

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

When to discard your medicine

Discard Travatan 4 weeks after opening it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
Eye problems:
  • Redness of the eye(s)
  • Eye pain
  • Increased sensitivity to light
  • Eye discharge
  • Uncomfortable feeling in the eye(s)
  • Eye irritation
  • Abnormal sensation in eye(s)
  • Feeling that something is in your eye(s)
  • Reduced vision
  • Blurred vision
  • Dry eye
  • Excessive secretion of tears from the eye(s)
  • Headache
  • Throat irritation
  • Cough
  • Unusual weakness
  • Dark circles under eyes
  • Itchy eyes
Other problems:
  • Dizziness
  • Increase in blood pressure (symptoms: severe headache, dizziness, vision problems)
  • Difficulty sleeping
  • Low blood pressure (symptoms: dizziness, lightheadedness)
  • Hair colour changes
  • Diarrhoea
  • Vomiting
  • Feeling sick
  • Pain in Tummy
  • Joint pain
  • Uncomfortable feeling or pain in the muscles, bones, joints, ligaments, or tendons
Skin Problems:
  • Redness of the skin
  • Itching
  • Skin discolouration
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Eye problems
  • An eye problem that causes blue, brown or grey discoloration around the iris or on the white part of the eye
  • Problems or damage to cornea, having symptoms such as eye discomfort, redness, sensitivity to light
  • Eye disease with symptoms such as painful red eye, increased sensitivity to light
  • Buildup of fluid in the macula, an area at the back of the eye, with symptoms like blurred vision, distorted vision
  • Unwanted hollows of the upper eyelid
  • Problems with eyelashes such as eyelash discolouration, increased length, thickness, pigmentation, and/or number of lashes
  • Swelling to the eyelid
  • Eye swelling
Other problems:
  • Symptoms of allergic reaction may include shortness of breath, difficulty breathing, swelling of the face, lips, tongue or other parts of the body, rash, hives.
  • Depression
  • Anxiety
  • Buzzing, hissing, whistling, ringing or other persistent noise in the ear(s)
  • Unusual heartbeat
  • Fast heartbeat
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What Travatan contain

Active ingredient
(main ingredient)		Travoprost.
Other ingredients
(inactive ingredients)		Ethoxylated hydrogenated castor oil, boric acid, mannitol sodium chloride, propylene glycol, sodium hydroxide and/or hydrochloric acid (to adjust pH) polyquaternium-1 (preservative) and purified water.
Potential allergensNA

Do not take this medicine if you are allergic to any of these ingredients.

What Travatan looks like

Travatan is a clear, colourless, sterile and preserved solution that comes in LDPE or PP bottle.

Pack sizes: 1 x 2.5 mL and 3 X 2.5 mL.

Not all pack sizes or container types may be marketed.

Who distributes Travatan

Travatan is supplied in Australia by:

Novartis Pharmaceuticals Australia Pty Limited

ABN 18 004 244 160
54 Waterloo Road
Macquarie Park NSW 2113
Telephone No. 1800 671 203
www.novartis.com.au

Travatan is supplied in New Zealand by:

Novartis New Zealand Limited
PO Box 99102
Newmarket
Auckland 1149
New Zealand
Free Phone: 0800 354 335.

Australian Registration Number

AUST R: 173354

This leaflet was prepared in June 2025.

Internal document code

(tra071123c_v2) based on PI (tra071123i)

Published by MIMS August 2025

BRAND INFORMATION

Brand name

Travatan Eye Drops

Active ingredient

Travoprost

Schedule

S4

 

1 Name of Medicine

Travoprost.

2 Qualitative and Quantitative Composition

Travatan 0.004% eye drops contain 40 microgram/mL travoprost.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Eye drops, solution.
Travatan Eye Drops is a clear, colourless, sterile and preserved solution.

4 Clinical Particulars

4.1 Therapeutic Indications

Travatan Eye Drops are indicated to decrease elevated intraocular pressure in: ocular hypertension; open angle glaucoma.
Travatan Eye Drops may be used: as first line monotherapy; as adjunctive therapy.

4.2 Dose and Method of Administration

Instil one drop of Travatan Eye Drops in the conjunctival sac of the affected eye(s) each day. Optimal effect is obtained if the dose is administered in the evening.
If more than one topical ophthalmic medicinal product is being used, the medicines must be administered at least 5 minutes apart.
When substituting another ophthalmic antiglaucoma agent with Travatan Eye Drops, discontinue the other agent and start the following day with Travatan Eye Drops.

Instructions for patients.

In accordance with good clinical practice for the administration of eye drops, patients should be instructed to gently occlude the nasolacrimal ducts for two minutes after instillation.
Discard container 4 weeks after opening.

4.3 Contraindications

Travatan Eye Drops are contraindicated in patients with a known hypersensitivity to travoprost or any of the excipients in the product (see Section 6.1 List of Excipients).
Travatan Eye Drops are also contraindicated in pregnant women or women attempting to become pregnant (see Section 4.6 Fertility, Pregnancy and Lactation).

4.4 Special Warnings and Precautions for Use

Not for injection or oral ingestion.
Travatan Eye Drops have not been studied in patients with narrow-angle glaucoma.

Eye colour changes.

Travatan Eye Drops may gradually change the eye colour by increasing the number of melanosomes (pigment granules) in melanocytes. Before treatment is instituted patients must be informed of the possibility of these changes. Unilateral treatment can result in permanent heterochromia. The long-term effects on the melanocytes and any consequences thereof are currently unknown. The change in iris colour occurs slowly and may not be noticeable for months to years. It may be permanent. The change in eye colour has predominantly been seen in patients with mixed coloured irides, i.e. blue-brown, grey-brown, yellow-brown and green-brown; however, it has also been observed in patients with brown eyes. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery in affected eyes, but the entire iris or parts of it may become more brownish. After discontinuation of therapy, no further increase in brown iris pigment has been observed.

Periorbital and eyelid changes.

Periorbital and/or eyelid skin darkening has been reported in association with the use of Travatan Eye Drops.
Periorbital and lid changes including deepening of the eyelid sulcus have been observed with prostaglandin analogues.
Travatan Eye Drops may gradually change eyelashes in the treated eye(s); these changes include: increased length, thickness, pigmentation, and/or number of lashes.

Aphakic patients.

Macular oedema has been reported during treatment with prostaglandin F2α analogues. Use travoprost with caution in aphakic patients, pseudophakic patients with torn posterior lens capsule or anterior chamber lenses, or in patients with known risk factors for macular oedema.

Iritis and uveitis.

There is no experience of Travatan Eye Drops in inflammatory ocular conditions, inflammatory, neovascular, angle-closure or congenital glaucoma and only limited experience in open-angle glaucoma of pseudophakic patients and in pigmentary glaucoma.
Travatan Eye Drops should be used with caution in patients with active intraocular inflammation, as well as patients with predisposing risk factors for uveitis.

Contact lenses.

If patients continue to wear soft (hydrophilic) contact lenses while under treatment with Travatan Eye Drops they should remove their lens(es) prior to instilling Travatan Eye Drops in the affected eye(s) and should not insert their lens(es) until 15 minutes after instillation of the eye drops.

Instructions for patients.

In accordance with good clinical practice for the administration of eye drops, patients should be instructed to gently occlude the nasolacrimal ducts for two minutes after instillation.

Use in hepatic impairment.

Travatan Eye Drops have been studied in patients with mild to severe hepatic impairment. No dosage alteration is necessary in these patients.

Use in renal impairment.

Travatan Eye Drops have been studied in patients with mild to severe renal impairment (creatinine clearance as low as 14 mL/min). No dosage alteration is necessary in these patients.

Use in the elderly.

No dosage alteration in elderly patients is necessary.

Paediatric use.

The safety and effectiveness of Travatan Eye Drops in paediatric patients have not been established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The plasma protein binding of the active free acid form of travoprost is moderate (approximately 80%) and, therefore, drug-drug interactions involving protein binding are unlikely.
In clinical studies, travoprost 0.004% eye drops were used concomitantly with timolol or brimonidine eye drops without evidence of additional adverse interactions. Concomitant therapy with miotics or adrenergic agonists has not been evaluated.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are no human data on the effects of Travatan Eye Drops on male or female fertility. Travoprost had no effects on mating behaviour or fertility in male and female rats at SC doses up to 10 microgram/kg (equivalent to 54 times human exposure at the MRCD), although embryofetal resorption was increased at 10 microgram/kg (further information on effects on pregnancy is included under Use in pregnancy).
(Category B3)
Studies in animals with travoprost have shown reproductive toxicity. Travoprost and/or its metabolites crossed the placenta in rats. Travoprost was teratogenic in rats at IV doses of 10 microgram/kg/day, equivalent to 98 times the expected human exposure at the proposed dose; it increased the incidence of hydrocephaly and bone abnormalities (e.g. vertebral malformations). Travoprost was not teratogenic in rats at IV doses of up to 3 microgram/kg/day (29 times the expected human exposure) or in mice at SC doses of up to 0.3 microgram/kg/day (1.2 times the human exposure). When administered during organogenesis (gestation days 6 to 17), travoprost produced increases in postimplantation loss and early delivery in mice at SC doses of 1 microgram/kg/day (4 times the human exposure) and in rats at IV doses of 10 microgram/kg/day. Increased postimplantation loss also occurred in rats at SC doses of 10 microgram/kg/day (54 times the expected human exposure) administered from 2 weeks prior to mating to gestation day 7.
Travoprost Eye Drops, 0.003% administered to rabbits during organogenesis, appeared to increase incidence of foetal loss.
In rats administered travoprost from gestation day 7 to lactation day 21 by SC injection, abortions occurred at 0.72 microgram/kg/day (4 times the expected human exposure), and decreased gestation length and increased stillbirths (also see Use in lactation) occurred at ≥ 0.12 microgram/kg/day (0.65 times the expected clinical exposure).
No adequate and well-controlled studies have been performed in pregnant women. Travoprost may interfere with the maintenance of pregnancy. It should not be used by women during pregnancy or by women attempting to become pregnant.
 An animal study showed that travoprost and/or its metabolites were excreted in rat milk. Increased pup mortality and depressed pup growth and development occurred in rats subcutaneously administered travoprost to dams from gestation day 7 to lactation day 21 at ≥ 0.12 microgram/kg/day, corresponding to exposures 0.65 times the expected human exposure. There are no data on the excretion of travoprost into human milk or on the safety of travoprost exposure in infants. Because many drugs are excreted in human milk, nursing women who use Travatan Eye Drops should stop breast-feeding.

4.7 Effects on Ability to Drive and Use Machines

As with other ophthalmic medications, patients should be advised to exercise caution if they experience transient blurred vision following instillation of eye drops; patients should wait until their vision clears before driving or using machinery (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.8 Adverse Effects (Undesirable Effects)

In clinical studies involving over 4600 patients, Travatan Eye Drops preserved with polyquaternium-1 was administered once daily as monotherapy or adjunctive therapy to timolol 0.5%. No serious ophthalmic or systemic undesirable effects related to Travatan Eye Drops were reported in any of the clinical studies. The most frequently reported treatment related undesirable effect with Travatan Eye Drops monotherapy was hyperaemia of the eye (21.8%), which included ocular, conjunctival, or scleral hyperaemia. Hyperaemia was mild in 83.8% of those patients who experienced it. Almost all patients (98%) who experienced hyperaemia did not discontinue therapy as a result of this event. In phase III clinical studies ranging from 6 to 12 months in duration, hyperaemia decreased over time.
The following undesirable effects were assessed to be treatment related with Travatan Eye Drops monotherapy and are classified according to the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), or very rare (< 1/10,000) (see Table 1). Within each frequency grouping, undesirable effects are presented in decreasing order of seriousness.

Class effects.

As with other prostaglandin analogues, Travatan Eye Drops may gradually change eyelashes in the treated eye(s); these changes were observed in about half of patients in clinical trials and include: increased length, thickness, pigmentation, and/or number of lashes. However, fewer than 1% reported these as adverse events. The mechanism of eyelash changes and their long-term consequences are currently unknown.

Long-term clinical study.

In a postapproval long-term clinical study of 5 years duration involving 502 patients, travoprost 0.004% eye drops preserved with BAK were administered once daily. No serious ophthalmic or systemic undesirable effects related to travoprost 0.004% eye drops were reported in the clinical study. The most frequently reported treatment related undesirable effect with travoprost 0.004% eye drops was iris hyperpigmentation (29.5%). Consequently, classification of this effect has been updated from common to very common. The upward change in frequency category does not represent a safety concern but rather presents a more accurate representation of the expected frequency of this effect associated with long-term exposure to a prostaglandin analogue.
Hyperaemia of the eye assessed as related to the use of travoprost 0.004% eye drops was reported at an incidence of 10.0% with 2% of patients reporting hyperaemia of the eye discontinuing study participation due to the undesirable effect.
In addition, several new adverse reactions have been identified from this long-term clinical study that have not been reported previously in clinical trials with travoprost 0.004% eye drops as monotherapy. All of these effects have been classified as uncommon (≥ 1/1,000 to < 1/100) and are listed in Table 2.

Postmarketing experience.

The following adverse reactions have been reported during postmarketing clinical studies in 4081 patients with Travatan Eye Drops and are classified according to the subsequent convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000) and very rare (< 1/10,000) (see Table 3). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Additional adverse reactions identified from postmarketing surveillance include the following (see Table 4). Frequencies cannot be estimated from the available data. Within each system organ class adverse reactions are presented in order of decreasing seriousness.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

A single dose intravenous study in rats was conducted to elucidate maximal acute hazard. The dose employed was 250,000 times the proposed daily clinical exposure and over 5,000 times the possible exposure from the entire contents of one product container. No treatment related pharmacotoxic signs were present in the animals receiving travoprost.
If overdosage with Travatan Eye Drops occurs, treatment should be symptomatic.
A topical overdose of Travatan Eye Drops may be flushed from the eyes with warm tap water.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Travoprost is an ester prodrug of a prostaglandin F2α analogue. It is hydrolysed to the free acid, which acts with nanomolar potency as a selective, full agonist of the prostaglandin FP receptor, and reduces the intraocular pressure (IOP) by increasing the outflow of aqueous humour via trabecular meshwork and uveoscleral pathways.
Reduction of the IOP in man starts about 2 hours after administration and maximum effect is reached after 12 hours. Significant lowering of IOP can be maintained for periods exceeding 24 hours with a single dose.
The benzalkonium chloride (BAK) free Travatan Eye Drops showed a similar IOP lowering effect to the original travoprost 0.004% eye drops preserved with BAK in a clinical study in 340 patients with a 12 week treatment period.

Secondary pharmacology.

Travoprost slightly, but significantly, increased optic nerve head blood flow in rabbits following 7 days of topical ocular administration (1.2 microgram, once daily).

Clinical trials.

Clinical studies with the BAK free formulation of Travatan Eye Drops.

Pharmacokinetics.

A single pharmacokinetic study was conducted to compare the systemic pharmacokinetics of the active metabolite travoprost free acid (AL-5848) following topical ocular administration of the BAK free (polyquaternium-1 preserved) formulation of Travatan Eye Drops and the initially registered travoprost 0.004% eye drops preserved with BAK.
The systemic pharmacokinetics of AL-5848 were assessed after single and multiple dose topical ocular administration. AL-5848 plasma concentrations were below the limit of quantitation (LOQ = 0.0100 nanogram/mL) in 93.8% of all samples analysed after administration of Travatan Eye Drops, and in 97.5% of all samples analysed after administration of travoprost 0.004% eye drops. With such a large proportion of samples below the limit of detection, pharmacokinetic parameters were not calculated.
Low plasma concentrations of AL-5848 were consistent with the concentrations seen in studies supporting the initial registration of travoprost 0.004% eye drops.

Efficacy studies.

One randomised, double masked, parallel group, multicentre study was conducted to compare the efficacy of BAK free Travatan Eye Drops and travoprost 0.004% eye drops preserved with BAK. Patients (n = 371) with open angle glaucoma or ocular hypertension were treated with Travatan Eye Drops or travoprost 0.004% eye drops once daily in the evening. It was found that both products provide equal IOP control over a 24 hour period.
Statistically significant mean reductions from baseline in IOP were observed for both Travatan Eye Drops and travoprost 0.004% eye drops at all time points (p < 0.001). Mean IOP reductions from baseline ranged from 7.6 to 8.7 mmHg for Travatan Eye Drops and from 7.7 to 9.2 mmHg for travoprost 0.004% eye drops, corresponding to IOP reductions of 31% to 33%, and 30% to 34%, respectively. The IOP reductions seen with travoprost 0.004% eye drops in this study are consistent with its performance in other reported studies.
Travatan Eye Drops and travoprost 0.004% eye drops provide comparable IOP control, defined as IOP < 18 mmHg at any time point. The percentage of patients across study time points with IOP < 18 mmHg ranged from 42% to 64% in the Travatan Eye Drops group and from 44% to 62% in the travoprost 0.004% eye drops group.
This study also demonstrated that Travatan Eye Drops provides IOP reduction beyond 24 hours postdose, as shown previously for travoprost 0.004% eye drops. The IOP lowering efficacy of Travatan Eye Drops was shown to be as good as that of travoprost 0.004% eye drops up to 60 hours postdose.
The safety and efficacy of Travatan Eye Drops is further supported by the clinical studies reported with travoprost 0.004% eye drops.
Clinical studies with travoprost 0.004% eye drops preserved with BAK. Three randomised, double masked, active controlled, parallel, multicentre studies were conducted to demonstrate the efficacy of travoprost 0.004% eye drops as monotherapy. Table 5 provides summary information from each of these studies. These studies were designed as "noninferiority" studies, powered to detect a difference of ± 1.5 mmHg in intraocular pressure between treatments.
These studies conclusively demonstrate that monotherapy with travoprost 0.004% eye drops produce clinically relevant and statistically significant reductions in intraocular pressure; these reductions in pressure are maintained over a 12 month dosing period.
Travoprost 0.004% eye drops was noninferior to latanoprost eye drops 0.005% at all visits during the 12 month study. In addition, an earlier onset of intraocular pressure reduction and better intraocular pressure control throughout the day were observed in patients receiving travoprost 0.004% eye drops, compared to latanoprost eye drops 0.005%. However, these were not predefined study endpoints and have only been observed in this single study.
Travoprost 0.004% eye drops were statistically superior to timolol eye drops 0.5% at each IOP measurement time of day, when results were pooled across study visits in the intent to treat analysis for each of the 12 month, 9 month, and 6 month studies but was on most occasions within the predetermined 1.5 mmHg difference in intraocular pressure. Also, travoprost 0.004% eye drops were statistically superior to timolol eye drops 0.5% at all visits in the intent to treat analysis of the 12 month study, at 11 of 15 visits in the intent to treat analysis of the 9 month study, and at 11 of 13 visits in the intent to treat analysis of the 6 month study.
Travoprost 0.004% eye drops have also been studied as adjunctive therapy to timolol and brimonidine. A randomised, double masked, parallel, placebo controlled, multicentre study, involving 427 patients, was conducted in order to demonstrate the additional intraocular lowering effect of travoprost 0.004% eye drops when added to existing timolol eye drops 0.5% bd. Whilst on timolol alone, the patients had a mean IOP of 24-36 mmHg at 8 am and an IOP of 21-36 mmHg at 10 am and 4 pm on 2 days to be assessed as eligible for enrolment. Table 6 provides summary information from this study.
This study conclusively demonstrates that travoprost 0.004% eye drops produce clinically relevant and statistically significant intraocular pressure reductions, compared to placebo, when used adjunctively with timolol eye drops 0.5%.
Additional IOP lowering efficacy has also been demonstrated when travoprost eye drops is combined with brimonidine eye drops. A multicentre, randomised, double blind, placebo controlled, parallel group study compared travoprost 0.0015% eye drops combined with brimonidine 0.2% eye drops versus travoprost 0.0015% eye drops versus placebo. A total of 81 patients were enrolled into the study and the treatment phase was of 42 days duration. Combined treatment of travoprost with brimonidine 0.2% eye drops produced a statistically significant greater decrease to mean IOP at the 10 am time point compared to travoprost eye drops alone. There was a significant fall in IOP compared to placebo for all the travoprost groups.
There is limited experience with the use of travoprost 0.004% eye drops in previously untreated patients. In the three pivotal monotherapy studies, the percentage of randomised patients who reported no current glaucoma therapy was 29%. It is not known how many of those patients had received no prior therapy. All patients enrolled in these studies who were on current ocular hypotensive medications underwent a wash out period from 3 days to 3 weeks.

5.2 Pharmacokinetic Properties

Absorption.

Travoprost is absorbed into the eye following topical ocular administration where it is hydrolysed to the active free acid. Following administration of 1.2 microgram 3H-travoprost in rabbits, the highest concentrations of radioactivity are found in the cornea, conjunctiva, aqueous humour and iris ciliary body. Maximum levels were observed 0.5-2 hours after instillation. Radioactivity concentrations in most ocular tissues declined with half-lives of less than 2 hours (> 10 h in cornea and lens). Systemic exposure is low. Maximum plasma concentrations of 0.08 nanogram equivalent/g were observed at 0.5 hours and declined rapidly thereafter.

Distribution.

Following topical ocular administration of Travatan Eye Drops to healthy volunteers, low systemic exposure to active free acid was demonstrated. Due to the low plasma concentrations and rapid elimination following topical dosing, the elimination half-life of active free acid in man could not be determined.

Metabolism.

The metabolic pathways of the acid parallel those of endogenous PGF2α and are characterised by reduction of the 13-14 double bond, oxidation of the 15-hydroxyl and β-oxidative cleavage of the carboxylic acid chain.

Excretion.

Travatan Eye Drops has been studied in patients with mild to severe hepatic impairment and in patients with mild to severe renal impairment. No dosage adjustment is necessary in these patients.

5.3 Preclinical Safety Data

Nonclinical data, obtained through in vitro studies with human conjunctiva epithelial cells and in vivo in rats and rabbits, demonstrate that polyquaternium-1 has significantly lower ocular toxicity than benzalkonium chloride.

Genotoxicity.

Travoprost did not cause gene mutation in bacteria or chromosomal aberrations in bone marrow cells of mice and rats. A slight increase in mutation frequency was observed in one of two mouse lymphoma L5178Y assays.

Carcinogenicity.

Long-term studies in mice and rats at SC doses up to 100 microgram/kg/day did not provide any evidence of carcinogenic potential. These doses correspond to exposure levels over 200 times human exposure at the maximum recommended clinical dose (MRCD), based on plasma active drug levels.

6 Pharmaceutical Particulars

6.1 List of Excipients

Ethoxylated hydrogenated castor oil, boric acid, mannitol, sodium chloride, propylene glycol, sodium hydroxide and/or hydrochloric acid (to adjust pH), polyquaternium-1 (preservative) and purified water.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C.
Discard container 4 weeks after opening.

6.5 Nature and Contents of Container

Travatan Eye Drops 0.004%: Available in LDPE or PP bottle. Pack sizes: 1 x 2.5 mL and 3 x 2.5 mL.
Not all pack sizes or container types may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Travoprost is a clear to slightly opalescent, colourless to yellow oil. Travoprost is practically insoluble in water (approximately 44 ppm).

Chemical structure.


Chemical name: (5Z,13E)-(9S,11R,15R)-9,11,15-Trihydroxy-16-(m-trifluoromethylphenoxy)-17,18,19,20-tetranor-5,13-prostadienoic acid, isopropyl ester.
Empirical formula: C26H35F3O6.
Molecular weight: 500.56.

CAS number.

157283-68-6.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (Schedule 4).

Summary Table of Changes